武汉大学泰康生命医学中心孙磊研究组发现，异构体的使用作为一个独特的调控层驱动营养反应性代谢适应。这一研究成果于2025年2月11日发表在国际顶尖学术期刊《细胞—代谢》上。

转录组调节对营养环境的代谢适应至关重要。

然而，同工异构体的作用，一个关键的转录组成分，尚未完全了解。本研究概述了小鼠和猴子跨越不同代谢状态的主要代谢器官的同型图像调节的景观。他们的深入分析确定了许多异构体损伤事件，这些事件受到营养挑战的复杂影响，并且在很大程度上独立于基因表达调控。对小鼠和猴子的比较分析强调了数百个保守的异构体事件，这些事件对不同物种的营养挑战表现出一致的反应，并与人类的代谢特征相关。当分析营养调节事件中的剪接因子结合基序时，HuR成为脂肪细胞中异构体网络的主要协调者，这在脂肪组织特异性敲除和ap2启动子驱动的转基因基序模型中得到了验证。

总之，他们的研究结果为代谢调节中的同工异构体损伤提供了一个全面的视角，为未来的功能研究奠定了基础。

附：英文原文

Title: Isoform usage as a distinct regulatory layer driving nutrient-responsive metabolic adaptation

Author: Jia Li, Chaoqun Cai, Wei Wen Teo, Kai Shin Chin, Yadanar Than Naing, Shengren Song, Franklin Nelson, Li Qiang, Dan Xu, Lei Sun

Issue&Volume: 2025-02-11

Abstract: Transcriptome modulation is essential for metabolic adaptation to nutrient environments. However, the role of isoform usage, a crucial transcriptome component, is not yet fully understood. This study outlines the landscape of isoform-usage modulations across major metabolic organs in both mice and monkeys, spanning diverse metabolic states. Our in-depth analysis identifies numerous isoform-usage events, intricately influenced by nutrient challenges and largely independent of gene expression regulation. Comparative analyses of mice and monkeys highlight hundreds of conserved isoform events that exhibit consistent responses to nutrient challenges across species and correlate with human metabolic traits. When analyzing splicing factor-binding motifs in nutrient-regulated events, HuR emerges as the predominant orchestrator of the isoform network in adipocytes, which is validated using an adipose tissue-specific knockout and an Ap2-promoter-driven transgenic mouse model. In summary, our results offer a comprehensive perspective on isoform usage in metabolic regulation, setting a platform for future functional inquiries.

DOI: 10.1016/j.cmet.2025.01.009

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00009-9